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DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration

DNA methylation based prognostic factor for patients with clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we identified survival-related DNA methylation sites based on the differentially methylated DNA CpG sites between normal renal tissue and ccRCC. Then, these surviv...

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Autores principales: Liu, Xiao-Ping, Ju, Lingao, Chen, Chen, Liu, Tongzu, Li, Sheng, Wang, Xinghuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593608/
https://www.ncbi.nlm.nih.gov/pubmed/33178689
http://dx.doi.org/10.3389/fcell.2020.572628
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author Liu, Xiao-Ping
Ju, Lingao
Chen, Chen
Liu, Tongzu
Li, Sheng
Wang, Xinghuan
author_facet Liu, Xiao-Ping
Ju, Lingao
Chen, Chen
Liu, Tongzu
Li, Sheng
Wang, Xinghuan
author_sort Liu, Xiao-Ping
collection PubMed
description DNA methylation based prognostic factor for patients with clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we identified survival-related DNA methylation sites based on the differentially methylated DNA CpG sites between normal renal tissue and ccRCC. Then, these survival-related DNA methylation sites were included into an elastic net regularized Cox proportional hazards regression (CoxPH) model to build a DNA methylation-based panel, which could stratify patients into different survival groups with excellent accuracies in the training set and test set. External validation suggested that the DNA methylation-based panel could effectively distinguish normal controls from tumor samples and classify patients into metastasis group and non-metastasis group. The nomogram containing DNA methylation-based panel was reliable in clinical settings. Higher total mutation number, SCNA level, and MATH score were associated with higher methylation risk. The innate immune, ratio between CD8(+)T cell versus Treg cell as well as Th17 cell versus Th2 cell were significantly decreased in high methylation risk group. In inclusion, we developed a DNA methylation-based panel which might be independent prognostic factor in ccRCC. Patients with higher methylation risk were associated genomic alteration and poor immune microenvironment.
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spelling pubmed-75936082020-11-10 DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration Liu, Xiao-Ping Ju, Lingao Chen, Chen Liu, Tongzu Li, Sheng Wang, Xinghuan Front Cell Dev Biol Cell and Developmental Biology DNA methylation based prognostic factor for patients with clear cell renal cell carcinoma (ccRCC) remains unclear. In the present study, we identified survival-related DNA methylation sites based on the differentially methylated DNA CpG sites between normal renal tissue and ccRCC. Then, these survival-related DNA methylation sites were included into an elastic net regularized Cox proportional hazards regression (CoxPH) model to build a DNA methylation-based panel, which could stratify patients into different survival groups with excellent accuracies in the training set and test set. External validation suggested that the DNA methylation-based panel could effectively distinguish normal controls from tumor samples and classify patients into metastasis group and non-metastasis group. The nomogram containing DNA methylation-based panel was reliable in clinical settings. Higher total mutation number, SCNA level, and MATH score were associated with higher methylation risk. The innate immune, ratio between CD8(+)T cell versus Treg cell as well as Th17 cell versus Th2 cell were significantly decreased in high methylation risk group. In inclusion, we developed a DNA methylation-based panel which might be independent prognostic factor in ccRCC. Patients with higher methylation risk were associated genomic alteration and poor immune microenvironment. Frontiers Media S.A. 2020-10-15 /pmc/articles/PMC7593608/ /pubmed/33178689 http://dx.doi.org/10.3389/fcell.2020.572628 Text en Copyright © 2020 Liu, Ju, Chen, Liu, Li and Wang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Liu, Xiao-Ping
Ju, Lingao
Chen, Chen
Liu, Tongzu
Li, Sheng
Wang, Xinghuan
DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration
title DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration
title_full DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration
title_fullStr DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration
title_full_unstemmed DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration
title_short DNA Methylation-Based Panel Predicts Survival of Patients With Clear Cell Renal Cell Carcinoma and Its Correlations With Genomic Metrics and Tumor Immune Cell Infiltration
title_sort dna methylation-based panel predicts survival of patients with clear cell renal cell carcinoma and its correlations with genomic metrics and tumor immune cell infiltration
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593608/
https://www.ncbi.nlm.nih.gov/pubmed/33178689
http://dx.doi.org/10.3389/fcell.2020.572628
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